The present invention relates to a process for producing L-histidine by fermentation, and more specifically to a process for producing L-histidine by culturing an L-histidine producing mutant microorganism belonging to the genus Corynebacterium or Brevibacterium in a nutrient medium and recovering the L-histidine produced thereby. The mutants employed are endowed with a resistance to growth inhibition by RNA polymerase inhibitors or a requirement for adenine.
L-histidine is an important amino acid which is commercially useful as a food additive or medicament. Accordingly, it is an object of the present invention to provide an improved process for production of such amino acid on an industrial scale at low cost.
Heretofore, it has been known that histidine analog-resistant strains belonging to the genus Corynebacterium or Brevibacterium have an ability to produce a significant amount of L-histidine (U.S. Pat. No. 3,713,977). Attempts to increase the productivity of these L-histidine producing microorganisms by imparting additional properties to them have also been made. For example, a process using strains endowed with a resistance to a purine analog or a pyrimidine analog is proposed in Japanese Published Examined Patent application No. 18798/1977. Another process using strains endowed with a requirement for arginine, methionine, tryptophan, phenylalanine, tyrosine, leucine, lysine or uracil is disclosed in U.S. Pat. No. 3,875,001. A further process using strains endowed with a resistance to sulfa drugs is disclosed in Japanese Published Unexamined Patent application No. 49490/1975. Yet another process using strains endowed with a resistance to 5-methyltryptophane, .alpha.-amino- .beta.-hydroxyvaleric acid, imidazole or aminotriazole is proposed in Japanese Published Unexamined Patent application No. 49491/1975. In Japanese Published Unexamined Patent application No. 69292/1975, a process is proposed using strains endowed with a requirement for threonine, proline, shikimic acid, xanthine or guanine. Furthermore, a process using strains endowed with a resistance to cobalamine is disclosed in Japanese Published Unexamined Patent application No. 70591/1975.
Although the processes exemplified above result in improved yields of L-histidine, the production yields of such processes, nevertheless, are comparatively low from a commercial application standpoint. Thus, a need exists for a process for producing L-histidine in higher yields at low cost.
To this end, it has now been found that L-histidine productivity of an L-histidine producing microorganism belonging to the genus Corynebacterium or Brevibacterium is greatly improved when such microorganism is endowed with a resistance to growth inhibition by RNA polymerase inhibitors or a requirement for adenine. Heretofore, it was not recognized that the productivity of L-histidine could be improved by endowing an L-histidine producing microorganism with either of such traits.